Schizophrenia treatments

• How is dopamine synthesised?

  Dopamine is synthesised from the amino acid tyrosine
• how is tyrosine converted to DOPA?

  tyrosine hydroxylase
• how is DOPA converted to dopamine?

  DOPA decarboxylase
• How is dopamine transported into vesicles?

  By vesicular monoamine transportes (VMAT)
• how is the action of dopamine terminated?

  • dopamine can travel away from the synapse
  • can be taken back up into pre-synaptic nerve terminals by dopamine transporters (DAT)
  • can be metabolised by enzymes
• What receptors do antipsychotics act at?

  Dopamine subtype D2 receptors
• Where are d1 and d5 receptors found

  Presynaptic nerve terminals
• where are d2, d3 and d4 receptors found?

  they are found both pre-synaptically and post-synaptically
• how many dopamine pathways are there?

  four
• what is the mesocortical pathway responsible for?

  cognitive control, motivation, emotion
• what is the mesolimbic pathway responsible for?

  reward
• what is the nigrostriatal pathway responsible for?

  movement
• what is the tuberohypophyseal pathway responsible for?

  prolactin release (breast milk production)
• what are the two types of antipsychotics?

  typicals and atypicals
• what receptors do typical (first gen) antipsychotics target?

  D2 dopamine receptors
• what receptors do atypical (second gen) antipsychotics target?

  d2 dopamine receptors and 5-HT2a receptors
• 4 examples of typical antipsychotics

  chlorpromazine

  fluphenazine

  haloperidol

  flupentixol
• features of typicals

  effects take days to develop

  only treat the positive symptoms

  can induce severe side effects
• features of atypical antipsychotics?

  produce fewer side effects

  more effective at treating negative symptoms
• d2 antagonism of atypical antipsychotics

  Atypical antipsychotics antagonise d2 receptors to a lesser extent than the typicals (lower potency)
• four examples of atypical antipsychotics

  clozapine

  olanzapine

  risperidone

  aripiprazole
• what type of antipsychotic has greater risk of side effects?

  typical antipsychotics induce side effects to greater extent than the atypicals due to greater potency and efficacy
• side effects of antipsychotics

  extra-pyramidal side effects

  antipsychotic malignant syndrome

  increased prolactin secretion

  weight gain

  sedation

  hypotension

  anticholinergic effects
• pyramidal and extra-pyramidal tracts

  Descend from the brain to the spinal cord
• function of pyramidal and extra-pyramidal tracts

  both tracts are involved in controlling movement
• pyramidal tracts

  pass through the pyramids of the medulla and directly innervate the motor neurones (involved in generation of muscle movement)
• extrapyramidal tracts 


  pass alongside the medulla and act to modulate and regulate movement (fine-tuning)
• what are the pyramidal and extra-pyramidal tracts controlled by?

  controlled by nigrostriatal pathway in the basal ganglia
• what can extra-pyramidal side effects resemble?

  Parkinson’s disease - slowness of movement and bradykinesia
• Extra-pyramidal side effects - rigidity

  Mask like face

  bradykinesia - slowness in movement and initiation of movement
• extra-pyramidal side effects - dystonias

  spasms of the face and neck muscles
• extra-pyramidal side effects - akathisia

  motor restlessness
• extra-pyramidal side effects - tardive dyskinesias

  tic-like movements

  worm-like movements

  appear late in the disorder
• antipsychotic malignant syndrome 


  life threatening disorder characterised by muscles cramps and tremor, fever, unstable autonomic system
• antipsychotic malignant syndrome - muscle cramps and tremor 


  caused by blockade of d2 receptors in basal ganglia
• antipsychotic malignant syndrome - fever 


  due to hypothalamic dopamine blockade
• antipsychotic malignant syndrome - unstable autonomic system 


  increased muscle activity can lead to rhabdomyolysis (muscle breakdown), leads to increased white blood cell count, metabolic acidosis, hypertensive crisis
• prolactin secretion

  prolactin promotes milk production
• what causes prolactin secretion?

  tuberohypophyseal pathway blockade
• symptoms of prolactin secretion

  breast swelling and milk secretion (in men too!)

  period cessation